Carbon isotope analysis has been applied in a variety of fields, including assessment of environmental dynamics based on the carbon cycle, and historical and empirical research through radiocarbon dating. The natural abundances of carbon isotopes, which may vary with regional or environmental factors, are as follows: 98.89% for 12C (stable isotope), 1.11% for 13C (stable isotope), and 1×10−10% for 14C (radioisotope). These isotopes, which have different weights, exhibit the same chemical behavior. Thus, artificial enrichment of an isotope of low abundance and accurate analysis of the isotope can be applied to observation of a variety of reactions.
In the clinical field, in vivo administration and analysis of a compound labeled with, for example, radioactive carbon 14C are very useful for assessment of drug disposition. For example, such a labeled compound is used for practical analysis in Phase I or Phase IIa. Administration of a compound labeled with radioactive carbon 14C (hereinafter may be referred to simply as “14C”) to a human body at a very small dose (hereinafter may be referred to as “microdose”) (i.e., less than the pharmacologically active dose of the compound) and analysis of the labeled compound are expected to significantly reduce the lead time for a drug discovery process because the analysis provides findings on drug efficacy and toxicity caused by drug disposition.
Examples of the traditional 14C analysis include liquid scintillation counting (hereinafter may be referred to as “LSC”) and accelerator mass spectrometry (hereinafter may be referred to as “AMS”).
LSC involves the use of a relatively small table-top analyzer and thus enables convenient and rapid analysis. Unfortunately, LSC cannot be used in clinical trials because of its high 14C detection limit (10 dpm/mL). In contrast, AMS can be used in clinical trials because of its low 14C detection limit (0.001 dpm/mL), which is less than one thousandth of that of LSC. Unfortunately, the use of AMS is restricted because AMS requires a large and expensive analyzer. Since only several tens of AMS analyzers are provided in Japan, analysis of one sample requires about one week due to a long waiting time for samples to be analyzed. Thus, a demand has arisen for development of a convenient and rapid method of analyzing 14C.